Oiwake-cho, Kyoto 606-8502, Japan Running head: Hepatic metallothionein in Mg-deficient rats Key words: Ca deficiency: Liver Zn: Mg deficiency: Metallothionein: Rats: Zn transporter

Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, an Mg-deficient diet, a Ca-deficient diet, and an Mgand Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration, and the concentration of Zn in the liver. The hepatic level of Zip14 mRNA increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5, and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase the serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by up-regulation of Zip14 expression and increases the hepatic Zn concentration, leading to the enhancement of the MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases the hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase the hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.